Human monocytes release lymphokines upon stimulation with a variety of soluble or particulate agents. These include: phorbol esters (i.e., phorbol myristate acetate, PMA) , calcium ionophores (Ionomycin) , serum-treated zymosan (STZ) concanavalin A (Con A) , and, to a major degree, lipopolysaccharides (LPS) . Not all stimuli acted the same in terms of production of all lymphokines. Protein Kinase C activation or increased intracellular Ca2+ are common features of the actions of most, if not all, of these stimuli. Prevention of PKC activation by the use of staurosporine at doses which abrogated superoxide release or arachidonate release by stimuli which act via PKC, failed to inhibit either TNF or ILl release in response to TPA as well as Con A and LPS. STZ Release of arachidonic acid by the action of PLA2 or other-mediated release of TNF was largely unaffected. Selective inhibition of cyclooxygenase metabolite formation by indomethacin, or 5-lipoxygenase product generation by L663,536 (Merck), failed to inhibit lymphokine release in response to any stimuli, including LPS.